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A new study casts doubt on 80 years of research suggesting that restricting calories without shorting nutrition may extend lifespan. Co-author Rafael de Cabo, an experimental gerontologist at the U. S. National Institute on Aging, and his colleagues found that calorie restriction conferred some health benefits on monkeys, but did not extend their life span. “One thing that’s becoming clear is that calorie restriction is not the Holy Grail for extending the life span of everything that walks on earth,” said de Cabo.

In 1934, researchers at Cornell University observed that laboratory rats fed a severely reduced calorie diet containing all of the required nutrients lived up to twice as long as rats fed normally. Calorie restriction (CR) is one of the few methods shown to increase lifespan in a variety of species, including yeast, flies, worms, fish, rodents, and dogs. There has never been—and may never be—a credible long-term clinical trial in humans; so we don't know whether CR prolongs human life. One of the longest running scientific studies in rhesus monkeys (genetically closer to humans than rodents) was begun at the University of Wisconsin in 1989. That study is ongoing and reports from time to time. In 2009, the Wisconsin researchers reported finding a trend toward longer life, but nothing determinative.

Roy Walford, MD, and his student Richard Weindruch are two of the researchers most commonly associated with calorie restriction as a means of extending life span.

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That brings us to the NIA study reported online August 29, 2012, in the journal Nature.

In the experiment, two sets of monkeys, one group aged 1 to 14 and another 16 to 23, were fed 30% less than what they would normally eat. Their outcomes were compared with two control groups of monkeys fed a normal diet. The calorie restricted monkeys, in both age groups, lived no longer than their normally fed counterparts. “However, a potential effect on maximum lifespan [opposed to average lifespan] cannot be ruled out,” Rafael de Cabo and his colleagues wrote.

Health benefits were mixed. Male monkeys on the restricted diet had significantly lower cholesterol levels, but the females did not see the same benefit. Cutting back calories appeared to lower cancer rates, but it also triggered a slight increase in cardiovascular disease. Another promising outcome was that various aging-related diseases appeared slightly later in the calorie restricted animals.

The NIA study began in 1987, two years before the Wisconsin study. That’s important, because the average lifespan of rhesus monkeys is 30 years; maximum lifespan is about 40. Scientists have to wait a long time to measure a difference in life span. Two more years of study could be telling.

There were other important differences in the NIA study and the Wisconsin study.

The 2009 status report on the Wisconsin study showed that calorie restriction extended the lives of the monkeys—with an important proviso. Deaths from non-age related causes were excluded—eliminating about half of the monkeys studied. If those deaths were included, the life extension disappeared. Many, but not all, scientists believe this compromised their finding on longevity. (The NIA study also excluded deaths from acute conditions that do not have an age-related increase in risk, such as intestinal bloat or injury.)

Other differences between the two studies were less significant, but could still affect the outcome.

The Wisconsin control monkeys were allowed to eat as much as they wanted, while the NIA controls were given a set amount of food. The Wisconsin controls were fatter than those in the NIA study. The NIA researchers wrote that the slight calorie restriction on their controls may have actually given them a life extension advantage. In addition, their controls were fed a healthier diet than the Wisconsin control. For example, the NIA controls ate whole foods, while the Wisconsin controls were fed a purified diet. The NIA controls were also given vitamin and mineral supplements, while only the calorie restricted animals in the Wisconsin study received supplements.

Another difference was the origin of the monkeys in the two studies. The animals in the Wisconsin study came from India, while those in the NIA study came from India and China, which gave them greater genetic diversity.

Whatever the reason for the conflicting results, we are still a long way from knowing whether CR extends life in humans.

More than a few scientists are still optimistic that CR will live up to its early life-extension promise. Roy Walford’s protégé, Richard Weindruch, now 62 and a director of the Wisconsin study, remains hopeful. Even so, he admits that he is not very good at restricting his own calories. He says he might start trying harder. There is still hope at his age, he adds.